Abstract
Breast cancer susceptibility gene 1 (BRCA1) located at chromosome 17q12-21 is a classic tumor suppressor gene, and has been considered as a significant role in hereditary breast cancers. Moreover, numerous studies demonstrated the methylation status of CpG islands in the promoter regions of BRCA1 gene was aberrant in patients with sporadic breast tumors compared with healthy females or patients with benign diseases. However, these conclusions were not always consistent. Hence, a meta-analysis was performed to get a more precise estimate for these associations. Crude odds ratio with 95% confidence interval were used to assess the association of BRCA1 promoter methylation and the risk or clinicopathologic characteristics of breast cancers under fixed or random effect model. A total of 40 studies were eligible for this present study. We observed the frequency of BRCA1 promoter methylation was statistically significant higher in breast cancers than non-cancer controls. Furthermore, BRCA1 methylation was statistically associated with lymph node metastasis, histological grade 3, ER(-), PR(-), triple-negative phenotype, and decreased or lack levels of BRCA1 protein expression. In conclusion, this study indicated that BRCA1 promoter methylation appeared to be a useful predictive or prognostic biomarker for breast cancers in clinical assessment.
Highlights
Our meta-analysis included 40 eligible articles, among which 20 articles were analyzed for the frequency of BRCA1 promoter methylation in breast cancers compared with non-cancer controls, and 30 articles were analyzed for the association between BRCA1 promoter methylation and clinicopathological features
The results of our study confirmed that BRCA1 promoter methylation was significantly correlated with the increased risk of breast cancer and associated with lymph node metastasis, histological grade 3, estrogen receptor (ER)(-), progesterone receptor (PR)(-), triple-negative phenotype and BRCA1 protein expression, which indicated that BRCA1 promoter methylation may be utilized as an effective biomarker in the management of breast tumors
Our meta-analysis demonstrated that the prevalence of BRCA1 promoter methylation in the breast cancer group was statistically significant elevated in comparison with the control group
Summary
The following data were extracted: the first author’s name, publication year, original country, methods for detecting methylation, the frequency of BRCA1 promoter methylation in case and control groups, control characteristics, sample materials and so on. Stratified-analyses were conducted based on ethnicity, methods for detecting methylation and sample materials to explore the potential source of heterogeneity. We estimated potential publication bias with funnel plot and Egger’s linear regression test. The funnel plot was visual symmetrical and the P-value of Egger’s test was greater than 0.05, which indicated that there were no statistically significant publication bias. All statistical tests in the meta-analysis were two-tailed and P-value ⩽0.05 was considered statistically significant unless otherwise noted. Statistical analyses were performed with Review Manager 5.2 software recommended by Cochrane Collaboration and STATA software version 12.0
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